Osteonecrosis of the jaw induced by receptor activator of nuclear factor-kappa B ligand (Denosumab) - Review

Med Oral Patol Oral Cir Bucal. 2016 Jul 1;21(4):e431-9. doi: 10.4317/medoral.21044.


Background: Denosumab, an anti-resorptive agent, IgG2 monoclonal antibody for human Receptor activator of nuclear factor-kappa B ligand (RANKL), has been related to the occurrence of osteonecrosis of the jaws. Thus, the aim of this study was to review the literature from clinical case reports, regarding the type of patient and the therapeutic approach used for osteonecrosis of the jaws induced by chronic use of Denosumab.

Material and methods: For this, a literature review was performed on PubMed, Medline and Cochrane databases, using the keywords "Denosumab" "anti-RANK ligand" and "Osteonecrosis of jaw". To be included, articles should be a report or a serie of clinical cases, describing patients aged 18 years or over who used denosumab therapy and have received any therapy for ONJ.

Results: Thirteen complete articles were selected for this review, totaling 17 clinical cases. The majority of ONJ cases, patients receiving Denosumab as treatment for osteoporosis and prostate cancer therapy. In most cases, patients affected by ONJ were women aged 60 or over and posterior mandible area was the main site of involvement. Diabetes pre-treatment with bisphosphonates and exodontia were the most often risk factors related to the occurrence of this condition. Systemic and local antibiotic therapy with or without surgical debridement was the most used treatment for ONJ resolution.

Conclusions: It is concluded that the highest number of ONJ cases caused by the use of anti-RANKL agents occurred in female patients, aged 60 years or older, under treatment for osteoporosis and cancer metastasis, and the most affected region was the mandible posterior.

Publication types

  • Review

MeSH terms

  • Aged
  • Bisphosphonate-Associated Osteonecrosis of the Jaw*
  • Bone Density Conservation Agents / adverse effects*
  • Denosumab / adverse effects*
  • Diphosphonates
  • Female
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B
  • Osteonecrosis
  • RANK Ligand


  • Bone Density Conservation Agents
  • Diphosphonates
  • NF-kappa B
  • RANK Ligand
  • Denosumab